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Study Links Stem Cells in Marrow to Fertility

Women may possess a hidden cache of stem cells in the bone marrow that constantly replenish the ovaries with new eggs, a new study suggests.

The idea contradicts long-established scientific dogma that holds that a woman is born with a complement of eggs that must last throughout her reproductive life.

The theory, proposed by researchers at the Massachusetts General Hospital, would, if confirmed, have major implications for fertility treatments, but at present it has many critics.

The researchers, led by Jonathan Tilly, report in this week's issue of Cell that the cache of germ-line stem cells in the bone marrow send cells via the blood stream, to the ovaries, which signal to the marrow when new supplies are needed.

Their work depends mostly on experiments with mice but they also cite cases where women have received bone marrow transplants after chemotherapy and unexpectedly conceived -- the result, the researchers suggest, of receiving a new supply of oocyte-making cells from the new bone marrow.

The new theory, if true, would reinforce the view of the bone marrow as the ultimate repository of the body's regenerative powers. Blood cells are known to be renewed from stem cells in the marrow, as are those of bone, cartilage and fat, and some researchers believe the heart is also replenished from the marrow.

Dr. Tilly's team would now add the reproductive system to this list. He is exploring whether a similar system may exist in men to replenish the sperm-making stem cells of the testes.

But the idea has not yet won acceptance among other researchers in the field. At the annual meeting in Quebec this week of the Society for the Study of Reproduction, Dr. Tilly debated his theory with David Albertini of the Kansas University Medical Center. Dr. Albertini said the general reaction of his colleagues to Dr. Tilly's theory was "overwhelmingly negative."

Dr. Tilly, however, said that although Dr. Albertini had canvassed several laboratories working on the problem, none had reported any results disproving the theory. "There was nothing presented that refuted our work," Dr. Tilly said.

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Dr. Tilly's work has been published in two leading scientific journals whose reviewers presumably advised that the research had merit. In an article in Nature last year, he argued that there must be some source from which new oocytes are generated after birth. In the article in this week's Cell, he writes that he has tracked down this apparent new source of oocyte-making cells to the bone marrow.

No other scientist has yet published work confirming the Nature result. Dr. Tilly said it was still early for anyone to have repeated the complex experiments.

As for the general reaction to this theory, he said, "There is a level of skepticism by some, but we have cohorts of colleagues who believe in the work, so it depends who you ask."

In his new work with mice, Dr. Tilly has shown that cells from the bloodstream of a donor mouse will home in on the ovaries of a recipient mouse whose oocytes have been destroyed. But he has not yet accomplished the final stage of showing that the donated cells, which he believes are oocytes, can be fertilized and generate baby mice. This experiment will take several months to do properly, he said.

Dr. Kutluk Oktay, an expert on reproduction and fertility at the Weill Cornell Medical Center in New York, said that the amount of evidence presented in the Cell article was "pretty compelling to me," and that the skepticism of other researchers was to be expected, given that a longstanding dogma was being overturned.

Dr. Tilly's theory, if correct, would have far reaching implications for the treatment of infertility, for instance through techniques to stimulate the bone marrow into stepping up production of oocyte-making cells. A press release issued by the Massachusetts General Hospital quotes Dr. Tilly as saying, "We may be ushering in a new era in the clinical management of female infertility and menopause."

Dr. Albertini characterized that statement as "hyped beyond belief."

Dr. Oktay, on the other hand, said that if Dr. Tilly's work can be extended to people, "We might be looking at an end to menopause as we know it right now."

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A version of this article appears in print on July 28, 2005, on Page A00016 of the National edition with the headline: Study Links Stem Cells In Marrow To Fertility. Order Reprints|Today's Paper|Subscribe